Introduction Staphylococcus aureus (S. aureus) bacteraemia is a common and severe infection. With mortality rates ranging from 20–30% and long-term impairments in over a third of survivors, better treatments are urgently needed. Linezolid, a well-established treatment for pneumonia and complicated skin infections, has been shown in preclinical studies to strongly suppress S. aureus virulence factors critical to bacterial persistence and tissue damage. Hence, we aim to investigate whether the addition of linezolid to standard therapy in patients with S. aureus bacteraemia leads to an overall improvement in patient-relevant outcomes.Methods and analysis We will conduct a two-arm, parallel-group, multicentre, randomised controlled trial (Linezolid Plus Standard of Care) in 12 hospitals in Switzerland with blinded treating physicians, patients and outcome assessors. Hospitalised patients aged ≥18 years with S. aureus bacteraemia will be eligible. Patients will receive standard antibiotic treatment as prescribed by the treating physician. Within 72 hours of collection of the blood sample yielding the first positive blood culture, patients will be enrolled and randomised 1:1 to receive either adjunctive linezolid (600 mg orally two times per day for 5 days) or placebo. To determine patient-relevant outcomes, we implemented a comprehensive patient-representative consultation process. Consequently, we will use the desirability of outcome ranking (DOOR) established for S. aureus bacteraemia as the primary outcome at 90 days. The hierarchical composite DOOR outcome includes the following four components, ranked from most to least important: (1) survival, (2) return to level of function before S. aureus infection, (3) complications leading to treatment changes and serious adverse reactions; and (4) hospital length of stay. This approach will allow us to analyse the win ratio, that is, whether patients receiving linezolid have a better DOOR rank compared to patients in the placebo group. We calculated a target sample size of 606 patients providing 90% power at a two-sided significance level of 0.05.Ethics and dissemination Ethical approval was received from the Ethics committee for Northern and Central Switzerland (BASEC number 2025-00655). Eligible patients will be informed about the study by the local study team and asked for written consent if they wish to participate. For patients unable to provide informed consent, an appropriate substitute (ie, a close relative or a physician not involved in the research project) may make decisions based on the presumed wishes and the best interest of the patient. The patient’s own consent will be obtained as soon as their condition permits. Results will be published in peer-reviewed journals and in laymen's terms through various channels (social media, Swiss national portal HumRes).Trial registration number NCT06958835.

Background: Wrist osteomyelitis caused by Scedosporium apiospermum is exceedingly rare. Its indolent course and destructive potential may result in extensive bone loss and pose substantial diagnostic and therapeutic challenges. Methods: We report a case of chronic wrist osteomyelitis caused by Scedosporium apiospermum in a 68-year-old kidney-pancreas transplant recipient. Results: Following diagnosis, systemic antifungal therapy with voriconazole was initiated, and multiple surgical debridements were performed to achieve local disease control, resulting in a large defect of the carpus and distal forearm. Hand salvage was attempted using an osteocutaneous triple-barrel fibula flap. The postoperative course was complicated by congestion of the fibula skin island, which was managed with leech therapy. Subsequent infection with a multi-resistant Aeromonas spp. and Morganella morganii led to flap necrosis, ultimately requiring transradial forearm amputation. Conclusions: Destructive Scedosporium apiospermum osteomyelitis in immunocompromised patients is a major challenge for reconstructive surgeons. Interdisciplinary management is essential as mold eradication is only achievable through a combined surgical and antimicrobial approach. In advanced destructive osteomyelitis, the choice between limb salvage and amputation should be individualized, considering patient comorbidities, reconstructive risk, and patients' preferences. This case highlights the importance of balancing careful indication and patient counseling in complex clinical scenarios.

Background: Long-term suppressive antibiotic therapy (SAT) is a management strategy for periprosthetic joint infection (PJI) when eradication is unattainable. However, SAT is often associated with adverse events (AEs) that may impact quality of life. This study aimed to evaluate the prevalence and types of AEs, assess patient-reported tolerability, and identify patient- and antibiotic-related factors associated with AEs during SAT for PJI. Methods: A retrospective analysis of a prospectively established cohort of 30 patients receiving SAT for PJI following DAIR (Debridement, Antibiotics, and Implant Retention) or prosthesis exchange between 2019 and 2022 was conducted at a specialized septic surgery department. SAT was indicated for suboptimal surgery or absence of biofilm-active antibiotics and was administered for ≥ 6  months. Structured patient interviews and institutional records were used to capture AEs, treatment modifications, SAT discontinuation, infection-related complications, and subjective tolerability. Patients were stratified by sex, age, BMI, and antibiotic agent. Results: The median SAT duration was 55 weeks (interquartile range (IQR): 40-101). Non-serious AEs occurred in 97 % of patients ( n = 29 ), predominantly affecting the gastrointestinal tract ( n = 63 ), skin ( n = 35 ), and nervous system ( n = 25 ). Treatment modifications were required in 23 % of patients, most frequently with amoxicillin or cotrimoxazole. SAT discontinuation occurred in one patient (3 %) due to multiple AEs. Four patients (13 %) experienced SAEs related to persistent or recurrent infection rather than antibiotic toxicity. Median subjective tolerability was 8 out of 10 (IQR 6-8); 57 % of patients rated tolerability as "good", 37 % as "moderate", and 6 % as "poor". Conclusion: SAT for PJI is associated with a high prevalence of mild to moderate AEs, but treatment discontinuation is rare. Most patients report acceptable tolerability, and serious antibiotic-related complications are uncommon. Careful patient selection, individualized monitoring, and management of AEs are essential to optimize long-term outcomes.

Introduction Diagnostic and therapeutic management of patients with periprosthetic joint infections (PJIs) remains challenging. This national cohort aims to describe the epidemiology, clinical phenotypes, management strategies and outcomes of patients with PJI.Methods and analysis This is a national, multicentre, prospective, longitudinal, observational cohort study of patients who underwent revision for PJI of the hip, knee, shoulder, elbow or ankle. Participating centres are university or non-university tertiary healthcare facilities located in Switzerland. Episodes include likely and confirmed PJI, as defined by the European Bone and Joint Infection Society criteria. During routine clinical visits around revision surgery, data are collected and patients are followed-up thereafter for a minimum of 2 years. The primary objective is infection outcome and secondary objectives include functional outcome and patient satisfaction and evaluation of host, infection, microbiological and treatment factors associated with treatment failure and poor functional outcomes, both in the overall population and across subgroups. A minimum of 329 patients would be needed to have sufficient statistical power to carry out these analyses.Ethics and dissemination Ethical approval has been granted by the Research Ethics Committee under protocol number 2021-01791. All patients provide written informed consent for inclusion in the study. Study findings will be disseminated through publications in peer-reviewed journals and presented at national and international conferences in the fields of orthopaedics, infectious diseases and microbiology. We plan to leverage the platform within the cohort to conduct future studies and interventional trials.Trial registration number NCT07473089.

Background:Meningitis and encephalitis are severe infections of the central nervous system (CNS) causing substantial morbidity and mortality. Contemporary nationwide data on epidemiological trends and outcomes are limited. Methods:We conducted a nationwide, retrospective cohort study using hospital discharge data from the Swiss National Health Registry. All hospitalizations for infectious meningitis and encephalitis between January 2012 and December 2021 were included. We assessed temporal and age-specific trends, pathogen distributions, and in-hospital outcomes using descriptive statistics and multivariable regression analysis. Results:Among 23 426 identified hospitalizations (10 160 for meningitis; 13 266 for encephalitis), the overall incidence of CNS infections increased from 22 to 34 per 100 000 inhabitants between 2012 and 2019, followed by a marked decline in 2020-2021. For meningitis, this decline was driven by reductions in pneumococcal (∼65%) and enteroviral (∼90%) infections. Enteroviral and streptococcal meningitis rates were highest in children younger than 10 years, whereas Streptococcus pneumoniae, Listeria monocytogenes, tick-borne encephalitis virus, and varicella-zoster virus infections were more frequent in adults older than 50 years. Compared with viral meningitis, bacterial meningitis was associated with higher odds of intensive care unit admissions (odds ratio [OR], 8.40; 95% confidence interval [CI], 7.29 to 9.67) and in-hospital mortality (OR 4.23; 95% CI, 2.95 to 6.05). Similar risk patterns were observed for bacterial encephalitis. Conclusions:Nationwide hospitalization rates for CNS infections showed distinct temporal and age-specific patterns. Bacterial infections, particularly among older adults, were associated with substantially worse outcomes, underscoring the importance of early diagnosis, optimized treatment, and preventive strategies, including vaccination.

OBJECTIVES:To compare rates of infective endocarditis (IE) and major adverse cardiac events (MACE) in patients with TAVI, bioprosthetic (bio), and mechanical (mech) SAVR. METHODS:Population-based cohort study of inpatient adults undergoing TAVI, bioSAVR or mechSAVR for aortic valve stenosis between 2012 and 2021 in Switzerland. In 2 pairwise 1:1 propensity-score matched cohorts (TAVI versus bioSAVR and bioSAVR versus mechSAVR) we analysed the primary outcome of the incidence of IE and secondary outcomes including MACE. RESULTS:Among 18,253 patients undergoing aortic valve replacement (mean age 76.6±10.3 years, 43.8% female), the incidence rate (IR) of IE was highest in the first 3 months after the intervention (TAVI, bioSAVR, mechSAVR: 23.61, 18.87, 16.65 per 1000 person-years, respectively). After matching, the rate of IE was higher in patients undergoing TAVI versus bioSAVR (n=2329 pairs, HR 1.56 [95% CI, 1.12-2.18]; incidence rate difference [IRD] 3.84 [95% CI,1.29-6.39] per 1000 person-years), and higher in bioSAVR versus mechSAVR (n=773, HR 2.27 [1.24-4.15]; IRD 4.57 [1.29-7.85] per 1000 person-years). The HRs for MACE were 2.10 [1.90-2.33] and 2.09 [1.58-2.77], respectively. CONCLUSIONS:For patients undergoing aortic valve replacement for native aortic valve stenosis, TAVI was associated with higher rates of IE than bioSAVR, as was bioSAVR when compared with mechSAVR.

Background. The epidemiology of infective endocarditis (IE) is evolving, driven by an aging population and increased use of endovascular devices, and is associated with significant morbidity and mortality. This study aims to evaluate changes in microbiological trends and clinical outcomes in patients with IE over the past decade in Switzerland. Methods. This nationwide cohort study analyzed in-hospital claims data from patients hospitalized with IE in Switzerland between 2012 and 2021. We assessed incidence rates per 100 000 hospitalizations, categorizing them by common pathogens. The outcomes included in-hospital and 6-month mortality, admission to the intensive care unit, and length of hospital stay. Results. Among 15 255 hospitalizations with IE, the annual number of cases increased from 1361 in 2012 to 1636 in 2021. The most frequently diagnosed pathogens were Staphylococcus aureus (increasing from 19.8% to 30.0%, P-trend < .01) and Streptococcus species (from 17.6% to 24.4%, P-trend < .01). Infective endocarditis caused by Staphylococcus aureus was associated with the highest in-hospital (19.9%) and 6-month mortality (30.3%), and intensive care unit admission rates (44.2%), with no relevant changes over time. The longest length of hospital stay was observed in hospitalizations with IE caused by Enterococcus species (mean 23.9 days) and S. aureus (23.8 days). Conclusions. This nationwide cohort study showed an increase in IE hospitalizations from 2012 to 2021, primarily from S. aureus and Streptococcus species. Predominantly, S. aureus was associated with adverse outcomes that remained consistently high over time compared to other or unidentified pathogens.

The Swiss expert group published revised guidelines on the prevention and antibiotic prophylaxis against infective endocarditis in 2021. In this viewpoint article, the group reports on their experiences two years after implementing the new prevention concept, which included information flyers and antimicrobial prophylaxis cards. Challenges included communicating the concept and indications for antimicrobial prophylaxis to both high-risk patients and providers.

OBJECTIVES:The performance of synovial fluid biomarker D-lactate to diagnose septic arthritis (SA) and differentiate it from crystal-induced arthritis (CA), other non-infectious rheumatic joint diseases (RD) and osteoarthrosis (OA) was evaluated. METHODS:Consecutive adult patients undergoing synovial fluid aspiration due to joint pain were prospectively included in different German and Swiss centers. Synovial fluid was collected for culture, leukocyte count and differentiation, detection of crystals, and D-lactate concentration. Youden's J statistic was used to determine optimal D-lactate cut-off value on the receiver operating characteristic (ROC) curve by maximizing sensitivity and specificity. RESULTS:In total 231 patients were included. Thirty-nine patients had SA and 192 aseptic arthritis (56 patients with OA, 68 with CA, and 68 with RD). The median concentration of synovial fluid D-lactate was significantly higher in patients with SA than in those with OA, CA, and RD (p<0.0001, p<0.0001 and p<0.0001, respectively). The optimal cut-off of synovial fluid D-lactate to diagnose SA was 0.033 mmol/L with a sensitivity of 92.3 % and specificity of 85.4 % independent of previous antimicrobial treatment. Sensitivity and specificity of synovial fluid leukocyte count at a cut-off of 20,000 cells/µL was 81.1 % and 80.8 %, respectively. CONCLUSIONS:Synovial fluid D-lactate showed a high performance for diagnosing SA which was superior to synovial fluid leukocyte count. Given its high sensitivity and specificity, it serves as both an effective screening tool for SA and a differentiator between SA and RD, especially CA.

Gas gangrene is a rare presentation of a necrotizing fasciitis, caused by Clostridium perfringens, C. septicum and other clostridial species. With its rapid progression it is a potentially life-threatening infection, that poses as a challenge in the clinical management requiring an interdisciplinary approach. Here we present a 62-year-old woman, who developed neutropenic fever while undergoing chemotherapy for triple negative breast cancer. She presented with a high fever, reporting little pain in her left thigh accompanied by redness and induration locally. Subsequently the patient developed pain and redness of the back of the left hand. The initial findings suggested cellulitis and immediate empiric treatment with intravenous meropenem was started. Despite the antibiotic treatment the patient rapidly developed septic shock along with progression of the local infection. Emergency surgical debridement revealed extensive necrosis of the soft tissues including extensive myonecrosis of the thigh. On the left hand an extensive debridement was performed, the left lower limb could not be preserved and exarticulation of the left hip was required. Microbiologically C. septicum was isolated in different samples, confirming gas gangrene. As there was no local entry portal on the skin, hematogenous seeding from intestinal translocation in this neutropenic patient was suspected. The empiric antibiotic treatment was tailored to intravenous penicillin and complemented with clindamycin for toxin inhibition. Following radical debridement and antibiotic treatment, the patient could be stabilized. After repetitive debridement wound closure was achieved and the patient was discharged for rehabilitation. Antibiotic treatment was continued for four weeks. This rare case of gas gangrene in a neutropenic patient shows the complexity in the diagnostic and therapeutic management of necrotizing soft tissue infections in immunocompromised patients. It particularly highlights the importance of an interdisciplinary management with fast recognition of the disease and rapid, if needed radical, surgical debridement as well as tailored antibiotic treatment for a successful outcome.

BackgroundTransfusion-related acute lung injury (TRALI) is a rare life-threatening complication of blood product transfusion. Intravenous immunoglobulin (IVIG)-related TRALI is scarcely reported.Case presentationA 63-year-old male patient suffering from multiple sclerosis treated with half-yearly rituximab infusions, was hospitalized due to dry cough, daily fever and shivering for seven days despite antibiotic therapy. Because of the history of COVID-19 one month prior without the symptoms having improved since, persistent bilateral multifocal areas of ground glass opacities in chest computed tomography and positive SARS-CoV-2 PCR from bronchoalveolar lavage with a cycling time of 30.1 COVID-19 due to long-shedding SARS-CoV-2 under immunosuppression with rituximab was diagnosed. He received treatment with nirmatrelvir und ritonavir and because of diagnosed IgG deficiency additionally a single dose of 20 g IVIG. During the IVIG infusion, the patient acutely developed tachycardia, hypotension, fever, chills, and hypoxemic respiratory failure due to pulmonary edema. TRALI was promptly diagnosed, and the patient was transferred to the intensive care unit for non-invasive ventilation for less than 24 h. The patient was discharged home from regular ward 72 h later in a good general condition and no remaining symptoms of TRALI.ConclusionIVIG-related TRALI is a rare but life-threating condition and prompt recognition is lifesaving. Due to an increased use of IVIG not only in long-shedding SARS-CoV-2, an increase of TRALI incidence is expected.

AIM OF THE STUDY:The first and second waves of the COVID-19 pandemic led to a tremendous burden of disease and influenced several policy directives, prevention and treatment strategies as well as lifestyle and social behaviours. We aimed to describe trends of hospitalisations with COVID-19 and hospital-associated outcomes in these patients during the first two pandemic waves in Switzerland.METHODS:In this nationwide retrospective cohort study, we used in-hospital claims data of patients hospitalised with COVID-19 in Switzerland between January 1st and December 31st, 2020. First, stratified by wave (first wave: January to May, second wave: June to December), we estimated incidence rates (IR) and rate differences (RD) per 10,000 person-years of COVID-19-related hospitalisations across different age groups (0-9, 10-19, 20-49, 50-69, and ≥70 years). IR was calculated by counting the number of COVID-19 hospitalisations for each patient age stratum paired with the number of persons living in Switzerland during the specific wave period. Second, adjusted odds ratios (aOR) of outcomes among COVID-19 hospitalisations were calculated to assess the association between COVID-19 wave and outcomes, adjusted for potential confounders.RESULTS:Of 36,517 hospitalisations with COVID-19, 8,862 (24.3%) were identified during the first and 27,655 (75.7%) during the second wave. IR for hospitalisations with COVID-19 was highest during the second wave and among patients above 50 years (50-69 years: first wave: 31.49 per 10,000 person-years; second wave: 62.81 per 10,000 person-years; RD 31.32 [95% confidence interval [CI]: 29.56 to 33.08] per 10,000 person-years; IRR 1.99 [95% CI: 1.91 to 2.08]; ≥70 years: first wave: 88.59 per 10,000 person-years; second wave: 228.41 per 10,000 person-years; RD 139.83 [95% CI: 135.42 to 144.23] per 10,000 person-years; IRR 2.58 [95% CI: 2.49 to 2.67]). While there was no difference in hospital readmission, when compared with the first wave, patients hospitalised during the second wave had a lower probability of death (aOR 0.88 [95% CI: 0.81 to 0.95], ARDS (aOR 0.56 [95% CI: 0.51 to 0.61]), ICU admission (aOR 0.66 [95% CI: 0.61 to 0.70]), and need for ECMO (aOR 0.60 [95% CI: 0.38 to 0.92]). LOS was -16.1 % (95% CI: -17.8 to -14.2) shorter during the second wave.CONCLUSION:In this nationwide cohort study, rates of hospitalisations with COVID-19 were highest among adults older than 50 years and during the second wave. Except for hospital readmission, the likelihood of adverse outcomes was lower during the second pandemic wave, which may be explained by advances in the understanding of the disease and improved treatment options.

Objectives: Shortening the duration of antibiotic therapy (DAT) for common infectious diseases may be an effective strategy to tackle antimicrobial resistance. Shorter DAT has been proven safe and effective for community-acquired pneumonia (CAP), cellulitis, and cholangitis.Methods: In a retrospective multicentre quality-control study, medical records of 770 patients hospital-ized with CAP, cellulitis, and cholangitis at three tertiary care hospitals in Switzerland during 2017-2018 were randomly selected. Appropriateness of antibiotic treatment duration was assessed according to in-ternational and local guidelines.Results: Records of 271, 260, and 239 patients with CAP, cellulitis, and cholangitis were included, respec-tively. Median DAT was seven days (interquartile range [IQR] 6-9), ten days (IQR 8-13), and nine days (IQR 6-13) in CAP, cellulitis, and cholangitis, respectively. DAT longer than recommended by local and international guidelines was observed in 32% and 37% of CAP patients, 23% and 70% of cellulitis patients, and 33% and 37% of cholangitis patients, respectively. Positive blood cultures (odds ratio [OR] = 2.42 (95% confidence interval [CI] 1.33-4.34]), infectious diseases consultation (OR = 1.79 [95% CI 1.05-2.78]), impaired renal function (OR = 0.99 [95% CI 0.98-1.0 0] per 1 ml/min / 1.73 m 2 increase in estimated glomerular filtration rate) and a higher degree of inflammation on admission (OR = 1.0 [95% CI 1.001- 1.005] per 10 mg/L increase in C-reactive protein) were independently associated with a DAT longer than recommended in international guidelines.Conclusions: DAT exceeded recommendations in a significant proportion of patients with mostly community-acquired infections.(c) 2022 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Background: Influenza-associated pulmonary aspergillosis (IAPA) is an important complication of severe influenza with high morbidity and mortality. Methods: We conducted a retrospective multicenter study in tertiary hospitals in Switzerland during 2017/18 and 2019/20 influenza seasons. All adults with PCR-confirmed influenza infection and treatment on intensive-care unit (ICU) for >24h were included. IAPA was diagnosed according to previously published clinical, radiological and microbiological criteria. We assessed risk factors for IAPA and predictors for poor outcome which was a composite of in-hospital mortality, ICU length of stay ≥7d, mechanical ventilation ≥7d or extracorporeal membrane oxygenation. Results: 158 patients (median age 64 years, 45% females) with influenza were included, of which 17 (10.8%) had IAPA. Asthma was more common in IAPA patients (17% vs. 4% in non-IAPA, p=0.05). Asthma (OR 12.0 (95% CI 2.1-67.2)) and days of mechanical ventilation (OR 1.1 (1.1 – 1.2)) were associated with IAPA. IAPA patients frequently required organ supportive therapies including mechanical ventilation (88% in IAPA vs. 53% in non-IAPA, p=0.001) and vasoactive support (75% vs. 45%, p=0.03) and had more complications including ARDS (53% vs. 26%, p=0.04), respiratory bacterial infections (65% vs. 37%, p=0.04) and higher ICU-mortality (35% vs. 16.4%, p=0.05). IAPA (OR 28.8 (3.3–253.4)), influenza A (OR 3.3 (1.4-7.8)) and higher SAPS II score (OR 1.07 (1.05—1.10)) were independent predictors of poor outcome. Interpretation: High clinical suspicion, early diagnostics and therapy are indicated in IAPA because of high morbidity and mortality. Asthma is likely an underappreciated risk factor for IAPA.

Objectives: The aim of this study was to identify and systematically analyze relevant literature on surgical site infections (SSIs) associated with implantable pulse generator (IPG) procedures for deep brain stimulation (DBS).Materials and Methods: In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic review and meta-analyses of 58 studies that reported SSI rates of 11,289 patients and 15,956 IPG procedures. A meta-analysis of proportions was performed to estimate the pooled proportion of SSIs across DBS procedures in general and to estimate the proportion of SSIs that occur at the IPG pocket. Moreover, a meta-analysis of odds ratio (OR) was conducted on those studies that reported their results of applying topical vancomycin powder during closure of the IPG wound.Results are presented as rates and OR with 95% CIs. Results: The pooled proportion of SSIs was 4.9% (95% CI, 4.1%-6.1%) among all DBS procedures. The dominant SSI localization was the IPG pocket in 61.2% (95% CI, 53.4%-68.5%). A trend toward a beneficial effect of vancomycin powder over standard wound closure was found with an OR of 0.46 (95% CI, 0.21-1.02). Most studies (79.1%) that reported their treatment strategy in case of SSI had a strict protocol of removal of the IPG, followed by antimicrobial treatment and reimplantation of the IPG once the SSI had been eradicated. Conclusions: The IPG pocket was identified as the main site of SSI after DBS procedures. Most studies recommend complete IPG removal, antimicrobial treatment, and reimplantation of an IPG once the SSI has been eradicated. Future studies are needed to clarify the role of alternative approaches (eg, topical vancomycin powder) in the prevention of SSI associated with IPG.

Background Patients with type 2 diabetes and obesity have chronic activation of the innate immune system possibly contributing to the higher risk of hyperinflammatory response to SARS-CoV2 and severe COVID-19 observed in this population. We tested whether interleukin-1b (IL-1b) blockade using canakinumab improves clinical outcome. Methods CanCovDia was a multicenter, randomised, double-blind, placebo-controlled trial to assess the efficacy of canakinumab plus standard-of-care compared with placebo plus standard-of-care in patients with type 2 diabetes and a BMI > 25 kg/m2 hospitalised with SARS-CoV2 infection in seven tertiary-hospitals in Switzerland. Patients were randomly assigned 1:1 to a single intravenous dose of canakinumab (body weight adapted dose of 450-750 mg) or placebo. Canakinumab and placebo were compared based on an unmatched win-ratio approach based on length of survival, ventilation, ICU stay and hospitalization at day 29. This study is registered with ClinicalTrials.gov, NCT04510493. Findings Between October 17, 2020, and May 12, 2021, 116 patients were randomly assigned with 58 in each group. One participant dropped out in each group for the primary analysis. At the time of randomization, 85 patients (74.6 %) were treated with dexamethasone. The win-ratio of canakinumab vs placebo was 1.08 (95 % CI 0.69-1.69; p = 0.72). During four weeks, in the canakinumab vs placebo group 4 (7.0%) vs 7 (12.3%) participants died, 11 (20.0 %) vs 16 (28.1%) patients were on ICU, 12 (23.5 %) vs 11 (21.6%) were hospitalised for more than 3 weeks, respectively. Median ventilation time at four weeks in the canakinumab vs placebo group was 10 [IQR 6.0, 16.5] and 16 days [IQR 14.0, 23.0], respectively. There was no statistically significant difference in HbA1c after four weeks despite a lower number of anti-diabetes drug administered in patients treated with canakinumab. Finally, high -sensitive CRP and IL-6 was lowered by canakinumab. Serious adverse events were reported in 13 patients (11.4%) in each group. Interpretation In patients with type 2 diabetes who were hospitalised with COVID-19, treatment with canakinumabin addition to standard-of-care did not result in a statistically significant improvement of the primary composite out-come. Patients treated with canakinumab required significantly less anti-diabetes drugs to achieve similar glycaemiccontrol. Canakinumab was associated with a prolonged reduction of systemic inflammation. Funding Swiss National Science Foundationgrant#198415and University of Basel. Novartis supplied study medication.

Background: A higher risk for severe clinical courses of coronavirus disease 2019 (COVID-19) has been linked to deficiencies of several micronutrients. We therefore studied the prevalence of deficiencies of eight different micronutrients in a cohort of hospitalized COVID-19-patients. Methods: We measured admission serum/plasma levels of vitamins A, B12, D, and E, as well as folic acid, zinc, selenium, and copper in 57 consecutively admitted adult patients with confirmed COVID-19 and analyzed prevalence of micronutrient deficiencies and correlations among micronutrient levels. Further, we studied associations of micronutrient levels with severe disease progression, a composite endpoint consisting of in-hospital mortality and/or need for intensive care unit (ICU) treatment with logistic regression. Results: Median age was 67.0 years (IQR 60.0, 74.2) and 60% (n = 34) were male. Overall, 79% (n = 45) of patients had at least one deficient micronutrient level and 33% (n = 19) had ≥3 deficiencies. Most prevalent deficiencies were found for selenium, vitamin D, vitamin A, and zinc (51%, 40%, 39%, and 39%, respectively). We found several correlations among micronutrients with correlation coefficients ranging from r = 0.27 to r = 0.42. The strongest associations with lower risk for severe COVID-19 disease progression (adjusted odds ratios) were found for higher levels of vitamin A (0.18, 95% CI 0.05–0.69, p = 0.01), zinc (0.73, 95% CI 0.55–0.98, p = 0.03), and folic acid (0.88, 95% CI 0.78–0.98, p = 0.02). Conclusions: We found a high prevalence of micronutrient deficiencies in mostly older patients hospitalized for COVID-19, particularly regarding selenium, vitamin D, vitamin A, and zinc. Several deficiencies were associated with a higher risk for more severe COVID-19 courses. Whether supplementation of micronutrients is useful for prevention of severe clinical courses or treatment of COVID-19 warrants further research.

Rubeli, Samuel MD; Conen, Anna MD, MSc; Diepers, Michael MD; Bernasconi, Luca PhD; Hasler, Paul MD; Mueller, Ruediger B. MDAuthor Information

Purpose: To compare temporal evolution of imaging features of coronavirus disease 2019 (COVID-19) and influenza in computed tomography and evaluate their predictive value for distinction. Methods: In this retrospective, multicenter study 179 CT examinations of 52 COVID-19 and 44 influenza critically ill patients were included. Lung involvement, main pattern (ground glass opacity, crazy paving, consolidation) and additional lung and chest findings were evaluated by two independent observers. Additional findings and clinical data were compared patient-wise. A decision tree analysis was performed to identify imaging features with predictive value in distinguishing both entities. Results: In contrast to influenza patients, lung involvement remains high in COVID-19 patients > 14 days after the diagnosis. The predominant pattern in COVID-19 evolves from ground glass at the beginning to consolidation in later disease. In influenza there is more consolidation at the beginning and overall less ground glass opacity (p = 0.002). Decision tree analysis yielded the following: Earlier in disease course, pleural effusion is a typical feature of influenza (p = 0.007) whereas ground glass opacities indicate COVID-19 (p = 0.04). In later disease, particularly more lung involvement (p < 0.001), but also less pleural (p = 0.005) and pericardial (p = 0.003) effusion favor COVID-19 over influenza. Regardless of time point, less lung involvement (p < 0.001), tree-in-bud (p = 0.002) and pericardial effusion (p = 0.01) make influenza more likely than COVID-19. Conclusions: This study identified differences in temporal evolution of imaging features between COVID-19 and influenza. These findings may help to distinguish both diseases in critically ill patients when laboratory findings are delayed or inconclusive.